pediatric abdominal pain assessment
DRUG REVIEW: LANSOPRAZOLE
DRUG REVIEW:LANSOPRAZOLE
Introduction
Proton pump inhibitors (PPIs) are the drugs of choice in the management of acid peptic disorders and are more effective than H2 receptor blockers. PPI – based antibacterial therapy regimens are the gold standard for the eradication of Helicobacter pylori which is an important agent in the pathogenesis of acid-peptic disease (1).
Chemistry and mechanism of action Lansoprazole is a substituted benzimidazole, 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl] methyl] sulfinyl] benzimidazole, a compound that inhibits gastric acid secretion. Its empirical formula is C16H14F3N3O2S with a molecular weight of 369.37. (2).Lansoprazole act by irreversibly blocking the hydrogen/potassium adenosine triphosphatase enzyme system (the H+/K+ ATPase, or, more common, gastric proton pump) of the gastric parietal cell. The proton pump is the terminal stage in gastric acid secretion, being directly responsible for secreting H+ ions into the gastric lumen, making it an ideal target for inhibiting acid secretion. (“Irreversibility” refers to the effect on a single copy of the enzyme; the effect on the overall human digestive system is reversible, as the enzymes are naturally destroyed and replaced with new copies.) Targeting the terminal-step in acid production, as well as the irreversible nature of the inhibition, results in a class of drugs that are significantly more effective than H2 antagonists and reduce gastric acid secretion by up to 99%. The lack of the acid in the stomach will aid in the healing of duodenal ulcers, and reduces the pain from indigestion and heartburn, which can be exacerbated by stomach acid. However, lack of stomach acid is also called hypochlorhydria, the lack of sufficient hydrochloric acid, or HCl. Hydrochloric acid is required for the digestion of proteins and for the absorption of nutrients, particularly of vitamin B12 and of calcium.(3)
Clinical studies Meta-analysis of lansoprazole 30 mg showed that it was more effective in producing healing at 2 and 4 weeks than ranitidine or famotidine. Lansoprazole also led to a greater reduction in the percentage of patients free of pain at 2 weeks. The efficacy of lansoprazole was not different from that of omeprazole (4). When lansoprazole was used as monotherapy, the mean Hp eradication was 6% in four studies. When lansoprazole was used in dual therapy with amoxicillin, pooled data from four trials employing various dosage schedules showed Hp eradication in 38.9% of patients. When lansoprazole was used in dual therapy with clarithromycin, the eradication rate was about 47.7% with lansoprazole 30 mg daily and 69.1% with lansoprazole 30 mg twice daily. When lansoprazole was used in triple therapy, Hp eradication rates ranged from 80% to 96%, with the best results obtained with a combination of lansoprazole, amoxicillin, and clarithromycin. Lansoprazole together with one or preferably two antibiotics is effective in Hp eradication. With the new macrolides, which have a lower rate of Hp resistance than metronidazole or tinidazole, we can expect to achieve eradication of Hp in all patients who are compliant with antibiotic therapy and infected with sensitive strains (5). Pharmacokinetics In general, the absorption of proton pump inhibitors is unaffected by co-administration with food. The rate of omeprazole absorption, however, is decreased by concomitant food intake. In addition, the absorption of lansoprazole and esomeprazole is decreased and delayed by food. It has been reported that these pharmacokinetic effects, however, have no significant impact on efficacy.[6] The elimination half-life of proton pump inhibitors ranges from 0.5–2 hours, however the effect of a single dose on acid secretion usually persists up to 2–3 days. This is because of accumulation of the drug in parietal cell canaliculi and the irreversible nature of proton pump inhibition. (7)
Drug Interactions: Lansoprazole is less likely than omeprazole to interact with other drugs. The absorption of certain drugs may be affected by stomach acidity, and, as a result, lansoprazole and other PPIs that reduce stomach acid also reduce the absorption and concentration in blood of ketoconazole (Nizoral) and increase the absorption and concentration in blood of digoxin (Lanoxin). This may lead to reduced effectiveness of ketoconazole or increased digoxin toxicity, respectively. (8) Adverse effects
In general, proton pump inhibitors are well tolerated, and the incidence of short-term adverse effects is relatively uncommon. The range and occurrence of adverse effects are similar for all of the proton pump inhibitors, though they have been reported more frequently with omeprazole. This may be due to its longer availability and, hence, clinical experience. Common adverse effects include: headache, nausea, diarrhea, abdominal pain, fatigue, dizziness.[9] Infrequent adverse effects include rash, itch, flatulence, constipation, anxiety, depression. Decreased vitamin B12 absorption may occur with long-term use.[8] Rarely PPI cause ‘idiosyncratic’ reactions such as erythema multiforme, pancreatitis, Stevens Johnson syndrome, and acute interstitial nephritis. [10]
It has been observed that gastric acid suppression, using H2-receptor antagonists and proton pump inhibitors, is associated with an increased risk of community-acquired pneumonia. It is suspected that acid suppression results in insufficient elimination of pathogenic organisms. Therefore, it has been suggested that patients at higher risk of pneumonia should be prescribed proton pump inhibitors only at lower doses and only when necessary. [11] PPIs have also been shown to raise risk of Clostridium difficile infection.[12]
Long-term use of proton pump inhibitors has been less studied. But, in a study of 135,000 people 50 or older, those taking high doses of PPIs for longer than one year have been found to be 2.6 times more likely to break a hip. Those taking smaller doses for 1 to 4 years were 1.2 to 1.6 times more likely to break a hip. The risk of a fracture increased with the length of time taking PPIs.[13]
Theories as to the cause of the increase are the possibility that the reduction of stomach acid reduces the amount of calcium dissolved in the stomach or that PPIs may interfere with the breakdown and rebuilding of bone by interfering with the acid production of osteoclasts.[14]
Also, the reduction of vitamin B12 (by raising homocysteine) may increase bone fragility, an effect that may be offset by the consumption, or by the co-packaging, of about 100 mcg of B12 with the PPI. A recent study has also suggested that proton pump inhibitors significantly decreased the effect of clopidogrel on platelets as tested by VASP phosphorylation. The clinical impact of these results must be assessed by further investigations, but a PPI treatment should not be added to the antiplatelet dual therapy without formal indication.[15]
Dosage and Administration The dose of lansoprazole (sold under the brand name Prevacid®) prescribed by your healthcare provider will vary depending on a number of factors, including: • The medical condition you are being treated for • Other medical conditions you may have • Other medications you may be taking. As is always the case, do not adjust your dose unless specifically instructed by your healthcare provider to do so.
For people experiencing gastroesophageal reflux disease (GERD) symptoms, the recommended lansoprazole dosage is 15 mg once a day for up to eight weeks. If the symptoms of GERD do not improve, your doctor may recommend GERD treatment with lansoprazole for another eight weeks. The recommended starting dosage of lansoprazole for the healing of erosive esophagitis is 30 mg once a day for up to eight weeks. Once the erosive esophagitis is healed, a daily dose of 15 mg may be recommended to prevent the return of the erosive esophagitis. The recommended starting dose of lansoprazole for the healing of duodenal ulcer is 15 mg once a day for four weeks. Once the ulcer has healed, your doctor may recommend a lansoprazole dosage of 15 mg once a day to prevent the ulcer from returning.
The recommended starting dose of lansoprazole to reduce the risk of a stomach ulcer (gastric ulcer) associated with non-steroidal anti-inflammatory drugs (NSAIDs) is 15 mg once a day for up to 12 weeks. The recommended starting dose of lansoprazole to heal stomach ulcer (gastric ulcer) associated with non-steroidal anti-inflammatory drugs (NSAIDs) is 30 mg once a day for up to eight weeks. Treatment to kill Helicobacter pylori (H. pylori) involves using two other drugs besides lansoprazole. This treatment is referred to as “triple therapy.” Triple therapy to kill H. pylori uses lansoprazole 30 mg twice a day plus amoxicillin 1,000 mg (twice daily) and clarithromycin 500 mg (twice daily). All three medications are taken for 10 or 14 days. In children ages 1 to 17, the recommended lansoprazole dose depends on the weight of the child. Consult your healthcare provider for pediatric dosing instructions.(16)
Conclusion Lansoprazole is a well-tolerated proton pump inhibitor. It has been shown to be effective in healing, symptom relief and prevention of relapse of peptic ulcers and gastrooesophageal reflux disease and can form part of effective H. pylori eradication regimens. It is an important alternative to H2 antagonists and an additional treatment option to other proton pump inhibitors in the management of acid related disorders.
References
1. Richardson P, Hawkey CJ, Stack WA. Proton Pump Inhibitors: Pharmacology and Rationale for use in Gastrointestinal Disorders. Drugs 1998;56:307-335
2. Rx list, the international drug index, pravacid, drug description.
3. Cooper BT, Chapman W, Neumann CS, Gearty JC (2006). “Continuous treatment of Barrett’s oesophagus patients with proton pump inhibitors up to 13 years: observations on regression and cancer incidence”. Aliment. Pharmacol. Ther. 23 (6): 727–33.
4. Poynard T, Lemaire M, Agostini H. Meta-analysis of randomized clinical trials comparing lansoprazole with ranitidine or famotidine in the treatment of acute duodenal ulcer. : Eur J Gastroenterol Hepatol. 1995 Jul;7(7):661-5.
5. LAMOULIATTE H. Adjuvant therapy for Helicobacter pylori eradication : role of lansoprazole in clinical studies. Lippincott Williams & Wilkins, Hagerstown, MD, ETATS-UNIS (1979).
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